Preparation of alicyclic-alkyl halides



Patented June 5, 1945 PREPARATION OF ALICYCLIC-ALKYL HALIDES Ralph P.Perkins, Midland, Mich., assignor to The Dow Chemical Company, Midland,Mich., a

corporation of ,Michigan No Drawingr. Original application November 15,

1940, Serial No. 365,768. Divided and this applicatlon July 23, 1942,Serial No. 452,053

12- Claims. (01. 260-611) This invention concerns an improved method ofpreparing alicyclic-alkyl halides. having the general formula:

which are obtainable by the method. It particularly concerns an improvedmethod of making beta-cyclohexyl-ethyl bromide and also the newcompound, bis- (beta-cyclohexyl-ethyl) ether, obtained in the process. i

It is known that beta-cyclohexyl-ethyl'bromide may be prepared in fairyield by heating betacyclohexyl-ethyl alcohol with an aqueous mixture ofsulphuric and hydrobromic acids. However, the organic reactant,beta-cyclohexyl-ethyl alcohol, is not readily available and the methods9 known for its preparation do not produce it in high yield. Forinstance, I-Iiers et al. J. A. C. S. 48, 1091 (1926) preparedbeta-cyclohexyl-ethyl bromide from cyclohexyl bromide, ethylene oxideand hydrobromic acid by first reacting the cyclohexyl bromide Withmagnesium to form cyclohexyl-magnesium bromide; reacting the latter withethylene oxide and hydrolyzing the product to obtainbeta-cyclohexyl-ethyl alcohol; and reacting said alcohol withhydrobromic acid in the presence of sulphuric acid as a condensing agentto obtain the beta-cyclohexyl-ethyl bromide product. The yield of theintermediate product,

cyclohexyl-ethyl alcohol, was only 53 per cent of theoretical in a smalllaboratory experiment and was indicated to be lower, i. e. only 44 percent, when prepared on larger scale. of beta-cyclohexyl-ethyl bromidefrom the .re-'

The yield action of hydrobromic acid with said alcohol was I per cent oftheoretical. Accordingly, the overall yield of beta-cyclohexyl-ethylbromide from the starting materials, cyclohexyl bromide, ethylene oxideand hydrobromic acid, was at best only 35 per cent of theoretical andwas lower when the reactions for. the preparation of the inter.-

mediate alcohol product were carried out on fairsized scale. I

It is an object of this invention to provide a new method ofmakingyalicyclic-alkyl halides having the general formula hereinbeforegiven whereby such products may be obtained in higher yields than ispossible by the method for their preparation heretofore known. Anotherobject is to provide certain new alicyclic -alkvl ethers, obtained inthe process, which ethers are useful as plasticizing agents for naturaland synthetic resins and also as organic solvents, particularly assolvents ,or bases for perfumes.

cyclohexyl-ethyl bromide may be prepared in good yield from startingmaterials which are readily available. Other objects will be apparentfrom the following description of the invention.

Alicyclic -n-alkyl halides are prepared according to the invention by:(1) dehydrating an aryln-alkyl alcohol to form the corresponding bis-(aryl-n-alkyl-l ether; (2) hydrogenating the latter to obtain a bis-(alicyc1ic-n-a1ky1-) ether; and (3) reacting said ether with a hydrogenhalide to obtain the alicyclic-n-alkyl halide product. Each reaction maybe carried out smoothly and nearly to completion'without excessiveby-product formation. For instance, in preparing betacyclohexyl ethylbromide from beta-phenylethyl alcohol by this series of steps orreactions, yields of per cent of theoretical and higherare readilyobtainable in each of the first two steps and yields of per cent andhigher are obtainable in the last step. The over-all yield ofbetacyclohexyl-ethyl bromide from the starting ma! etc.; and alkalimetal acid sulphates such as sodium or potassium acid sulphate. Thecondensing agent is usually employed in amount cor responding tobetweenZ and 10 per cent ofthe weight of the phenyl-ethyl alcohol, butmay A particular object is to provide a method whereby betabe used inlarger or in somewhat smaller proportion if desired. Water is preferablydistilled from the reaction mixture as it is formed. The removal ofwater may be facilitated, and the reaction thus furthered, by carryingthe reaction out in the presence of an inert water-immiscible liquid,suchas benzene, toluene, or ethylene chloride, etc., Which will distilltogether with the Water as a relatively low-boiling azeotrope.immiscible liquid may, of course, be introduced prior to, or during, thereaction and may be separated from the water in the distillate and bereturned continuously or intermittently to the reaction mixture. Thetime of heating necessary to complete the reaction is dependent upon thereaction temperature, the kind and proportion of condensing agent used,and upon whether or not an immiscible liquid is introduced to facilitateremoval of the water formed. However, when operating in accordance withthe preferred conditions just given, the reaction'ls usually completeafter 6 to 12 hours of heating. The reacted mix ture is preferablyneutralized or rendered slightly alkaline, e. g. by treatment withsodium'hydroxide, sodium carbonate or other basic compound, andfractionally distilled to separate the bis- (beta-phenyl-ethyl-) etherproduct. I

The ether so obtained is treated with an active hydrogenation catalyst,e. a. platinum, reduced nickel or cobalt, or .Raney nickel, or apromoted metal catalyst rich in nickel such as a reduced mixture of 80per cent Ni, per cent Fe, and 10-per cent Cu, and hydrogenated inaccordance with usual procedure. The hydrogenation catalyst is usuallyemployed in amount corresponding to between 2 and 8 per cent of theweight of the ether, but may be used in other proportions if desired.The hydrogenation is usually carried out witha reduced nickel catalystin a bomb or.

other closed reactor with agitation at temperatures between 100 C. and160 C. under a hydrogen pressure of between 200 and 500 pounds persquare inch, gauge, but other temperatures and pressures may be used.After completing the hydrogenation, the pressure is released and themixture is filtered to recover the catalyst therefrom and distilled toseparate the bis-(betacyclohexyl-ethyl-) ether product.

The bis-(betacyclohexyl-ethyl-) ether is reacted with hydrogen bromideto form the desired beta-cyclohexyl-ethyl bromide end-product. Eithersubstantially anhydrous hydrogen bromide or an aqueous mixture ofhydrobromic acid and another acid capable of combining with the waterformed, e. g. sulphuric acid, may be used in the reaction. The hydrogenbromide or hydrobromicacidv is advantageously used in amountcorresponding to the molecular equivalent or more of the ether. Whenanhydrous hydrogen bromide is to be used in the reaction, the ether ispreferably saturated, e. g. at room temperature or lower, with gaseoushydrogen bromide and is thereafter gradually heated to its boilingpoint, or thereabout. When an aqueous hydrobromic acid solution is to beemployed in the reaction, the ether is preferably dissolved inconcentrated sulphuric acid, the mixture is cooled, e. g. to C. orlower, and the aqueous hydrobromic acid solution is added graduallywhile maintaining the mixture in cooled condition. The hydrobromic acidsolution is employed in amount corresponding to 2 moles or more,preferably between 2 and 4 moles, of hydrogen bromideper mole of theether. One mole or more of sulphuric acid is used per mole of water inthe reaction mix- The waterture. The mixture is permitted to stand atroom temperature or thereabout for from 1 to 6 hours, after which it isgradually heated to boiling. Regardless of whether hydrogen bromide oraqueous hydrobromic acid is used, the reaction mixture is heated to itsboiling point or thereabout for from 4 to 10 hours. However, thereaction may be carried out at other temperatures, e. g. at temperaturesbetween 60 C. and C. When operating at temperatures abov the normalboiling temperature of the mixture, it is.

necessary, of course, thatthe reaction be carried "out under pressure,e. g. in a bomb or autoclave.

After completing the reaction, the mixture is cooled and the organic andaqueous layers thereof are separated. Th organic layer may be washedwith concentrated sulphuric acid, then with water, or preferably with anaqueous alkali solution, to remove dissolved acid, and distilled toseparate the beta-cyclohexyl-ethyl bromide product, I

Other alicyclic-n-alkyl halides may advantageously be prepared fromcorresponding aromaticn-alkyl alcohols .by similar procedures. For instance, if hydrogen iodide, instead of hydrogen bromide is employed inthe particular application of the process described above, the finalproduct is beta-cyclohexyl-ethyl iodide. Similarly, hydrogen chloridemay be used instead of hydrogen bromide or hydrogen iodide in theabove-described application of the process to obtainbeta-cyclohexyl-ethyl chloride as the prodnot. However, hydrogenchloride is less active than hydrogen bromide, and the latter is usuallysomewhat less'active than hydrogen iodide in reacting withbis-(alicyclic-alkyl) ethers to form the alicyclic-alkyl halideproducts." In using hydrogen chloride in such reaction, the latter isadvantageously carried out under pressure at temperatures as high orhigher than those employed When using hydrogen bromide as a reactant.

The invention may also advantageously be applied in preparingbeta-(2-methyl-cyclohexyl-) ethyl chloride or bromide -or iodide frombeta- (ortho-methyl-phenyl-) ethyl alcohol; beta:

(3-methyl-cyclohexyl-) ethyl chloride, bromide in whichthe principle ofthe invention has-been applied, but are not to be construed as limitinth invention.

, Example 1 A mixture of 976 grams of beta phenyl-ethyl alcohol and 48.8grams of sodium acid sulphate monohydrate (NaHSO4H2O) was heated underreflux with stirring at temperatures between 68 C. and 178 C. for 14hours, while graduallydistilling off water formed by the reaction. Atotal of 63 grams of water was distilled from the mixture during theheating. A small amount of oily material distilledtogether with thewater,-but

. this was separated fromthe aqueous layerzof the distillate andreturned continuously to the reactionmixture. The mixture was thereaftercooled,

washed successively with water, an aqueous sodiumncarbonate solution,and water and dractionally distilled under vacuum. .There were obtained95.5 grams of unreacted phenyl-ethyl alcohol and 726.1 grams ofbis-(beta-phenyl-ethyl) ether which distilled at 190 C.-195 C. at 20millimeters absolute pressure. The ether product slightly yellow andcontained a small amount of dissolved sulphur. dioxide. It was washedwith a'solution of 35 grams of sodium carbonate in 2501.cubiccentimetersl ofwater, then with 1-liter of water alone, and.redistilled. There was obtained 710.6 grams of nearly colorless purifiedbis-(beta-phenyl ethyl) ether. The yield was 87.1 per cent oftheoreticaLbased on the phenylethyl alcohol consumed. ,This ether, washydrogenated soon after its preparation, since I had, in other;experiments, observed that if permitted to standit tends to absorb airand quite rapidly becomes contaminated with organic peroxides which arepoisonous toward hydrogenation catalysts.. -The hydrogenation wascarried out by charging albomb with 250 grams of the bis- (beta- Iphenyl-ethyl) ether and. 12.5grams of a hydrobis-(beta-cyclohexyl-ethyl) ether distilling at 1 180; 10. 1849 C: atmillimeters pressure was obtained. The yield was 83.6 per cent oftheoretical. The bis-(beta-cyclohexyl-ethyl) ether is a colorless liquidcompound which boils at 164 C.-165 C. at 10 millimeters pressure, or atapproximately 220 C. at 100 millimeters pressure. It has the Specificgravity, D =0.909 and the index of refraction 11. =1.472. Gaseoushydrogen bromide was passed into 203.4 grams of thebis-(beta-cyclohexy-ethyl) ether until 141.3 grams of hydrogen bromidewas absorbed. The

hours. It was then cooled to room temperature and again saturated withgaseous hydrogen bromide, only 27.2 grams of the latter being absorbedin this treatment. The resultant mixture was boiled under reflux for 3.5hours. It was then cooled, washed thoroughly with water' andfractionally distilled. There was obtained 295.3 grams ofbeta-cyclohexyl-ethyl bromide, distilling at temperatures between 101 C.and 103 C. at 25 millimeters pressure. The yield was 90.4 per cent oftheoretical based on the bis-(beta-eyclohexyl-ethyl) ether employed. Theover-all yield of beta-cyclohexyl-ethyl bromide, based on materialsconsumed in the series of reactions, was higher than 65 per cent oftheoretical.

Example 2 A mixture of 340.2 grams of gamm'a-phenylpropyl alcohol and 17grams of sodium acid sulphate monohydrate was heated under reflux withstirring at temperatures ranging from 170 C. to 188 C. for about 7hours, while permitting water formed by the reaction to distill from themixture. Thelatter was than pcooled and-successive-' 1y washed withwaterandwith a hot aqueous sodium hydroxide solutionand distilled. There wereobtained 28 ,grams of unreacted gammae phenyl-propyl alcohol and 220.5grams of bis- (gamma-phenylspropyl) ether whichdistilled at temperaturesbetween 218 C. and 220 C. at 20 millimeters absolute pressure. The yieldof ether was approximately 66.5 per cent of theoretical, based on thegjamma-phenyl-propyl alcohol. 180 grams of the bis-(gamma-phenyhpropyl)ether was hydrogenated as. in Example, 1. There was obtained 151.6 gram's, or 80.3 per cent of the theoretical yield, ofbis-(gamma-cyclohexyl-propyl) ether. The latter is a colorless liquidcompound which boils at approximately 208 C.'210 C. at 20 millimetersabsolute pressure. It has the specific gravity D2s =0.897 and the indexof refraction n .470. A portion of the bis- (gamma-cyclohexyl-propyl)ether was .heated with concentrated sulphuric acid and anaqueoussolution of hydrobromic acid, whereby. gammacyclohexyl-propyl-bromidewas formed. The gamma-cyclohexyl-propyl-bromide product is a colorlessliquidboiling at 118 C.-l20 C. at 20 millimeters pressure, having, theindex of refraction n =L486 and the specific gravity, D25 5=1.196.

. EmampleB Bis-('beta-(para-methyl-phenyl-) ethyl) ether waspre'pared in81.9per cent of the theoretical yield byheating 340 grams ofbeta-(para-methylphenyl-) ethyl alcohol and 17 grams of sodium acidsulphate hydrate under reflux for 5 hours while distilling waterfromthemixture asit was formed. Said ether is a crystalline solid whichmelts at 50 c.-'51 c. and distills t temperasolution was graduallyheated to about 130 0., 5 where boiling occurred, and wasmaintained attemperatures between 130 C. and 132 C. for 4 tures between 220 C. and224 C. at 25 millimeters pressure. The bis-(beta-(para-methyl-phenyl-)ethylbether was hydrogenated by procedure similar to that described inExample 1, whereby bis- (beta-4-methyl-cyclohexyl-ethyl) ether wasobtained in 63 per cent yield. This ether is acolorless liquid compoundboiling at 205 C.207 C. at 25 millimeters pressure and having thespecific gravity, D25 =0.892 and the index of refraction n =1.467. Thebis-(beta-i-methyl-cyclohexylv ethyl) ether was reacted with hydrogenbromide as in Example 1, whereby beta-4-methyl-cyclohexyl-ethyl bromidewas obtained in approximately 59 per cent yield. Said product is acolorless liquid which boils at C.-111 C. at 20 millimeters pressure andhas the specific gravity, D2525=1,192, and the index of refraction,

This application is a division of my copending agpiigaglon, Serial No.365,768, filed November Other modes of applying the principle of thewherein R represents a member of the group consisting of hydrogen andlower alkyl radicals, n

imately 0.897 at 25 C.

is an integer greater than '1 and less'than sand the'ether oxygen atomis attached to a primal;

carbon atom of each C'nHZn radical.

"ZI'Kbis-'(alicyclic-alkyl) ether having the genera'l formulaz i Jwherein R represents a member of. the groupcons'isting-of hydrogen andvlower "alkyl radicals, CnH2 1t iS. a normalalkylenef radical, and 'nisan integer greater than 1 and less than 5'. v t

3. A bis- (a1icyc1i'ca1ky1) ether having the general formula:

wherein CnHZn is a normal alkylene radical and n is an integer greaterthan 1 and less than-5.

' '4. A bis-(cyclohexyl-alkyl) ether having the eneral formula: i

7. Bis-(betas4-methyl cyclohexyl-ethyl) lather, I

8. In a method of makinga'compourid haying the general formula:

wherein R represents amember'of the group consisting of hydrogen andlower alkyl radicals, Cal-I21} is a normal alkylene I acllcalhandrtflis" an integer greater than 1 and less than'5, the' step whichconsists inhydrogenating abis iaryl -nalkyll ether to form thecorresponding bis-(alloy clic-n-glkyl) ether. h I

9'. In a method of making' an ether haringithe general formula? Iwherein n is an'integer greater'than 1- and less than 5 and the etheroxygen atom isatt'ached "to a primary carbon atom of each C Hzn radical,the step which consists in hydrogenating a bis- (phenyl-n-alkyl) etherto form the corresponding bis-icyclo hexyl-alkyl) ether." "IQQ'In' ame'thoc i of' making bis-(bta-cygilohexyl-ethyl) ether; the step whichcohsist'sin' hya drogenating bis-(beta-phenyl-ethyl) 'ether. 11. Inamethod of making bis-'(gamma-cyclo hexyI-propyl) ether, the stepwhich'consists in hydrogenating bis- (gamma-phenyl-propyl) ether.

12; In a method of making bislhetaA-methylcyclohexyl-ethyl) ether, thestepwhieh consists in hydrogenating' bis-(beta-4 methyl-phnylethylyether; "f

- I RALPH P. PERKINsi

